Overactive Bladder (OAB)
Conditions
Interventions
Mirabegron tablets 25 mg or 50 mg (test product) and corresponding placebo
Mirabegron oral suspension with 8 mg/ml (test product) and corresponding
placebo
Sponsors
Astellas Pharma
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: Inclusion at Visit 1/Week -4 (Screening) 2. Subject has OAB defined according to the ICCS criteria. 4. Subject weighs at least 11 kg at screening. 5. Subject is able to take the IP in accordance with the protocol. 6. Subject agrees to drink an adequate fluid volume during urine collection weekends, as instructed by the investigator. 7. Subject and subject*s parent(s)/legal guardian(s) agree that the subject will not participate in another interventional study while participating in the present study. 8. Subject and subject*s parent(s)/legal guardian(s) are willing and able to comply with the study requirements and with the concomitant medication restrictions. 9. At least 1 of the following conditions apply: a. Not a woman of childbearing potential (WOCBP) b. WOCBP who agrees to follow the contraceptive guidance from the time of informed consent/assent through at least 30 days after final IP administration. 10. Female subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final IP administration. 11. Female subject must not donate ova starting at first dose of IP and throughout the study period and for 30 days after final IP administration. 12. Male subject with female partner(s) of childbearing potential (including breastfeeding partner[s]) must agree to use contraception throughout the treatment period and for 30 days after final IP administration. 13. Male subject must not donate sperm during the treatment period and for 30 days after final IP administration. 14. Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 30 days after final IP administration. Additional Inclusion at Visit 3/Week 0 (Baseline) 15. Subject must have a micturition frequency of at least 8 times (on average) per day, in the 7 days prior to visit 3/week 0 (baseline), as recorded in the bladder e-diary. 16. Subject must have at least 1 daytime incontinence episode (on average) per day, during the 7-day period before visit 3/baseline, as recorded in the bladder e-diary. 17. Subject whose symptoms are not satisfactorily controlled with urotherapy and still fulfills the inclusion/exclusion criteria will enter the study.
Exclusion criteria
Exclusion criteria: Exclusion at Visit 1/Week -4 (Screening) 1. Subject has extraordinary daytime only urinary frequency according to the ICCS definition * This applies to a toilet-trained child who has the frequent need to void that is associated with small micturition volumes solely during the day * The daytime voiding frequency is at least once per hour with an average voided volume of < 50% of expected bladder capacity (EBC) (typically 10% to 15%) * Incontinence is rare and nocturia is absent Subject has 2. an uroflow indicative of pathology other than OAB 3. monosymptomatic enuresis 4. dysfunctional voiding 5. bladder outlet obstruction, except if successfully treated 6. anatomical anomalies (surgically treated or untreated) that affect lower urinary tract function 7. Subject with hematuria on dipstick test. In the case of hematuria on dipstick test in a female during menstruation, the test can be repeated before randomization (after the end of menstruation) 8. Subject with diabetes insipidus Subject has 9. kidney or bladder stones 10. suffered from chronic UTI or has had more than 3 UTIs in the 2 months prior to visit 1/week -4 (screening) 11. a pulse > 99th percentile for age 12. stage 2 hypertension or subject has stage 1 hypertension that is not well controlled, as defined by the 2017 American Academy of Pediatrics Clinical Practice Guidelines 13. QTcF > 440 msec on screening ECG or a risk of QT prolongation (e.g., hypokalemia, long QT syndrome [LQTS] or family history of LQTS or exercise-induced syncope) 14. Subject*s aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is >= 2 × upper limit of normal (ULN) or total bilirubin (TBL) is >= 1.5 × ULN according to age and sex (subjects with Gilbert*s syndrome are excepted from the bilirubin threshold) Subject has 15. mild or moderate renal impairment (estimated glomerular filtration rate according to the modified Schwartz of < 60 mL/min per 1.73 m2) 16. a symptomatic (symptoms can include pain, fever, hematuria, new onset foul-smelling urine) UTI. Note: if the UTI is treated successfully (clinical recovery: confirmed by dipstick test and repeated dipstick test after 14 days [both should be negative]), the subject can be rescreened 17. a history or presence of any malignancy 18. Subject uses any drugs that are sensitive cytochrome P450 2D6 (CYP2D6) substrates with a narrow therapeutic index or sensitive P-glycoprotein (P-gp) substrates after the start of washout 19. Subject is using or has used prohibited prior and/or concomitant medication(s) Subject has 20. known or suspected hypersensitivity to mirabegron or any components of the formulations used 21. participated in another clinical study (and/or subject has received any investigational therapy within 30 days (or 5 half-lives of the drug, or the limit set by national law, whichever is longer) prior to visit 1/week -4 (screening) 22. Subject received urinary catheterization within 2 weeks prior to screening 23. Constipation as defined by the Rome IV criteria that cannot be successfully treated prior to study entry 24. Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening 25. Subject has any condition which makes the subject unsuitable for study <b
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Endpoints Primary * Change from baseline at the end of the 12 week treatment period: * Mean number of micturitions per 24 hours | — |
Secondary
| Measure | Time frame |
|---|---|
| Endpoints Secondary * Change from baseline at the end of the 12 week treatment period: * Mean volume voided per 24 hours * Maximum volume voided * Mean number of daytime incontinence episodes per 24 hours * Mean number of nighttime incontinence episodes per 24 hours * Mean number of daytime micturitions per 24 hours * Number of dry (incontinence free) days per 7 days at the end of the 12 week treatment period * Nature, frequency and severity of AEs * Clinical laboratory tests (hematology, biochemistry and urinalysis) * Vital signs (blood pressure and pulse) * Routine 12-lead ECG * PVR volume * Acceptability and palatability questionnaire * Appropriate pharmacokinetic parameters will be calculated based on the population pharmacokinetic model used Table continued on next page Exploratory * Percentage of subjects with a reduction in daytime incontinence episodes ( | — |
Countries
Netherlands
Outcome results
None listed